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Tuesday, August 23, 2016

Targeted therapies and tumor lysis syndrome

Novel targeted therapies are being approved in clinical trials for many hematologic malignancies. Tumor lysis syndrome (TLS) is being noticed as a novel side effect of many of these agents. A recent review in AJH summarizes the various drugs that have led to TLS as a potential side effect of targeted therapies.

TLS was most common in drug trials dealing with patients with acute leukemias, high grade non Hodgkin’s lymphomas, mantle cell lymphomas, CLL and myeloma. Some of the risk might be tumor related rather than the drug but below are the drugs that could be potential TLS promoting.
Incidence of TLS based on clinical trials for novel targeted therapies

Alvocidib (cyclin dependent kinase inhibitor) – 42% in poor risk AML patients, 13% in CLL patients
Venetoclax( ABT-199)( small molecule B cell lymphoma/leukemia 2 inhibitor)- 2.7-8.9% in CLL
Dinaciclib( cyclin dependent kinase inhibitor)- 15% in patients with AML or ALL and another 15% in CLL
Ibrutinib( Bruton kinase inhibitor)- 6.7% in CLL patients
Dasatinib( BCR-ABL tyrosine kinase inhibitors)- 4.2% in patients with ALL
Lenalidomide( immunomodulatory agent)- 3-4% in CLL patients
Obinutuzumab( anti CD20 agent)- 3-4.8% in CLL patients
Oprozomib( proteasome inhibitor)- 2.4% in various hematologic malignancies
Brentuximab vedotin( anti cd30 antibody)- 1.7% in anaplastic large cell lymphoma patients
Carfilzomib( proteasome inhibitor)- 1% in myeloma patients

Not much found in the two listed below
Idelasib( phosphatidylinositol 3-kinase inhibitor)- No TLS in CLL patients
Ofatumumab( anti CD20 agent)-No TLS in CLL patients



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